High bioavailability, short half-life, and metabolism into hydromorphone-3-glucuronide following single intramuscular and intravenous administration of hydromorphone hydrochloride to great horned owls (Bubo virginianus)

Abstract

Abstract OBJECTIVE To determine the pharmacokinetic parameters of hydromorphone hydrochloride and its metabolite, hydromorphone-3-glucuronide (H3G), after a single IV and IM dose in great horned owls (Bubo virginianus). ANIMALS 6 healthy adult great horned owls (3 females and 3 males). PROCEDURES A single dose of hydromorphone (0.6 mg/kg) was administered once IM (pectoral muscles) and IV (left jugular) with a 6-week washout period between experiments. Blood samples were collected at 5 minutes and 0.5, 1.5, 2, 3, 6, 9, and 12 hours after drug administration. Plasma hydromorphone and H3G concentrations were determined with liquid chromatography–tandem mass spectrometry, and a noncompartmental analysis was used for the determination of pharmacokinetic parameters. RESULTS Hydromorphone had a high bioavailability of 170.8 ± 37.6% and rapid elimination after IM administration and rapid plasma clearance and a large volume of distribution after IV administration. Mean Cmax was 225.46 ± 0.2 ng/mL at 13 minutes after IM injection. Mean volume of distribution and plasma drug clearance was 4.29 ± 0.5 L/kg and 62.11 ± 14.6 mL/min/kg, respectively, after IV administration. Mean t1/2 was 1.62 ± 0.36 and 1.35 ± 0.59 hours after IM and IV administration, respectively. The metabolite H3G was readily measured shortly after administration by both routes. CLINICAL RELEVANCE A single dose of 0.6 mg/kg was well tolerated in all birds. Hydromorphone rapidly attained plasma concentrations following IM administration and had high bioavailability and short t1/2. This study is the first to document the presence of the metabolite H3G in avian species, which suggests similar hydromorphone metabolism as in mammals.